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Colonic Motility (colonic + motility)

Distribution by Scientific Domains

Medical Sciences	91%

Selected Abstracts

Colonic motility in chronic ulcerative proctosigmoiditis and the effects of nicotine on colonic motility in patients and healthy subjects

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2001
B. Coulie
Background: Nicotine decreases diarrhoea and pain in ulcerative colitis without reducing inflammation. Aims: (i) To evaluate the effect of ulcerative proctosigmoiditis on motor functions of an uninflamed segment of descending colon; and (ii) to assess nicotine's effects on colonic motor functions in patients and healthy subjects. Methods: In healthy subjects (n=30) and patients with ulcerative colitis (13; 11 active, two quiescent colitis), we studied the effects of intravenous nicotine on colonic transit of solid residue by scintigraphy (healthy subjects) and on colonic motility in healthy subjects and 11 patients. Results: In ulcerative colitis, fasting colonic motility was increased, whereas motor response to a meal was significantly reduced; compliance was unchanged. In healthy subjects, high-dose nicotine induced transient high amplitude propagated contractions and relaxation of the descending colon followed by decreased phasic contractions. This dose also accelerated colonic transit. Low-dose nicotine (mimicking a transdermal nicotine patch) reduced colonic compliance in healthy subjects, but did not affect motor function in ulcerative colitis. Conclusions: Ulcerative proctosigmoiditis increases fasting colonic motility and reduces tone response to a meal in the descending colon without affecting colonic compliance, suggesting changes in physiological responses but not intrinsic wall properties. Nicotine has dose-dependent effects on colonic motor activity in healthy subjects. [source]

Effects of female steroid hormones on A-type K+ currents in murine colon

THE JOURNAL OF PHYSIOLOGY, Issue 2 2006
Elizabeth A. H. Beckett
Idiopathic constipation is higher in women of reproductive age than postmenopausal women or men, suggesting that female steroid hormones influence gastrointestinal motility. How female hormones affect motility is unclear. Colonic motility is regulated by ion channels in colonic myocytes. Voltage-dependent K+ channels serve to set the excitability of colonic muscles. We investigated regulation of Kv4.3 channel expression in response to acute or chronic changes in female hormones. Patch clamp experiments and quantitative PCR were used to compare outward currents and transcript expression in colonic myocytes from male, non-pregnant, pregnant and ovariectomized mice. Groups of ovariectomized mice received injections of oestrogen or progesterone to investigate the effects of hormone replacement. The capacitance of colonic myocytes from non-pregnant females was larger than in males. Net outward current density in male and ovariectomized mice was higher than in non-pregnant females and oestrogen-treated ovariectomized mice. Current densities in late pregnancy were lower than in female controls. Progesterone had no effect on outward currents. A-type currents were decreased in non-pregnant females compared with ovariectomized mice, and were further decreased by pregnancy or oestrogen replacement. Kv4.3 transcripts did not differ significantly between groups; however, expression of the potassium channel interacting protein KChIP1 was elevated in ovariectomized mice compared with female controls and oestrogen-treated ovariectomized mice. Delayed rectifier currents were not affected by oestrogen. In the mouse colon, oestrogen suppresses A-type currents, which are important for regulating excitability. These observations suggest a possible link between female hormones and altered colonic motility associated with menses, pregnancy and menopause. [source]

Ethanol Upregulates iNOS Expression in Colon Through Activation of Nuclear Factor-kappa B in Rats

ALCOHOLISM, Issue 1 2010
Chao Wang
Background:, Alcohol inhibits colonic motility but the mechanism is unknown. The goal of this study was to test the possibility that nuclear factor-kappa B (NF-,B) is involved in the upregulation of inducible nitric oxide synthase (iNOS) expression induced by ethanol in colon. Methods:, The isometric contraction of longitudinal muscle strips of proximal colon (LP) was monitored by polygraph. Western blot analysis was used to measure the amount of iNOS and I-,B in the cytoplasm and P65 in the nucleus. Immunohistochemistry was applied to locate iNOS in colon. Results:, Ethanol (87mM) inhibited the contraction of LP. Pretreatment of S-methylisothioure (SMT) (1 mM), a specific iNOS inhibitor, Pyrrolidine dithiocarbamate (PDTC) (10 mM) and BAY11-7082(10 mM), specific inhibitors of NF-,B significantly reversed the inhibitory effect of ethanol on LP contraction. Ethanol increased the amount of iNOS and content of NO in colon, and these effects were attenuated by pretreatment of PDTC. Following ethanol administration, the amount of I-,B in the cytoplasm decreased, but that of P65, the subunit of NF-,B in the nucleus, increased. The iNOS was located in the cell body of myenteric plexus in colon. Conclusion:, Ethanol inhibited the contraction of LP in colon mainly through activation of NF-,B, the subsequent upregulation of iNOS expression and increase of NO release in myenteric plexus. [source]

A dynamic model of colonic concentrations of delayed-release 5-aminosalicylic acid (Asacol)

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 11 2009
M. P. THORPE
Summary Backround, 5-ASA in a pH sensitive tablet (Asacol) is administered as three doses/day to treat ulcerative colitis. Once daily dosing may improve patient adherence. Simulation of colonic levels of 5-ASA can be used to compare dosing regimens. Aim, To create a dynamic model of colonic concentrations of delayed-release 5-aminosalicylic acid (Asacol). Methods, Using published data, we created a computer model with STELLA software to simulate amounts of colonic 5-ASA in the total colon, right, transverse, descending and sigmoid/rectum after daily and three time/day Asacol. Results, The model predicted similar total and regional amounts of 5-ASA with both regimens. Distribution of 5-ASA was 38% in the right colon, 33% in the transverse colon and 14% each in the descending and sigmoid/rectal colon. Simulated increases in colonic motility and defecation rate exaggerated this 5-ASA distribution, resulting in negligible amounts of 5-ASA in the sigmoid/rectal region. Conclusions, This computer model suggests that Asacol can be administered as a single daily dose. The model supports experimental and clinical observations that alternate dose or route of administration may be necessary to achieve adequate 5-ASA amounts in the distal colon during acute exacerbations of ulcerative colitis. This simulation cannot account for all sources of variability in the clinical setting, but provides a rationale for further investigation. [source]

Review article: uncomplicated diverticular disease of the colon

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 10 2006
L. PETRUZZIELLO
Summary Diverticular disease of the colon is the fifth most important gastrointestinal disease in terms of direct and indirect healthcare costs in western countries. Uncomplicated diverticular disease is defined as the presence of diverticula in the absence of complications such as perforation, fistula, obstruction and/or bleeding. The distribution of diverticula along the colon varies worldwide being almost always left-sided and directly related to age in western countries and right-sided where diet is rich in fibre. The pathophysiology of diverticular disease is complex and relates to abnormal colonic motility, changes in the colonic wall, chronic mucosal low-grade inflammation, imbalance in colonic microflora and visceral hypersensitivity. Moreover, there can be genetic factors involved in the development of colonic diverticula. The use of non-absorbable antibiotics is the mainstay of therapy in patients with mild to moderate symptoms, and the effect of fibre-supplementation alone does not appear to be significantly different from placebo, although no definite data are available. More recently, alternative treatments have been reported. Mesalazine acts as a local mucosal immunomodulator and has been shown to improve symptoms and prevent recurrence of diverticulitis. In addition, probiotics have also been shown to be beneficial by re-establishing a normal gut microflora. In this study, the current literature on uncomplicated diverticular disease of the colon is reviewed. [source]

Effect of alosetron on left colonic motility in non-constipated patients with irritable bowel syndrome and healthy volunteers

ALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 5 2002
C. H. M. Clemens
Background: Alosetron is a 5-hydroxytryptamine-3 receptor antagonist reducing symptoms in female patients with diarrhoea-predominant irritable bowel syndrome, and is known to increase the colonic transit time. Aim: To study the effect of alosetron on left colonic phasic motility in ambulant non-constipated patients with irritable bowel syndrome and healthy volunteers. Methods: In a double-blind, randomized, crossover design, 10 patients with irritable bowel syndrome and 12 sex- and age-matched volunteers were treated for two 7-day periods with alosetron, 4 mg b.d., or placebo b.d. On day 6 of each treatment period, a six-channel solid-state manometric catheter was positioned in the left colon and 24 h motility was studied on day 7. The periprandial phasic motility around dinnertime was evaluated in the descending and sigmoid colon. The high-amplitude propagated contraction frequency and characteristics were calculated. Results: Alosetron appeared to increase the overall periprandial frequency in the sigmoid colon (P=0.043) and the mean amplitude of colonic contractions in the descending colon (P=0.007). The high-amplitude propagated contraction frequency was higher on alosetron during the second half of the day for patients with irritable bowel syndrome (P=0.002), with increased mean propagation length of high-amplitude propagated contractions (P=0.001). The stool frequency (P=0.024) and stool consistency score (P=0.002) were decreased by alosetron. Conclusions: The 5-hydroxytryptamine-3 receptor antagonist alosetron marginally increased left colonic periprandial phasic motility. Alosetron increased the number and propagation length of high-amplitude propagated contractions, which were paradoxically accompanied by a decrease in stool frequency and a firming of stool consistency. [source]

Colonic motility in chronic ulcerative proctosigmoiditis and the effects of nicotine on colonic motility in patients and healthy subjects

Differential effects of CB1 neutral antagonists and inverse agonists on gastrointestinal motility in mice

NEUROGASTROENTEROLOGY & MOTILITY, Issue 7 2010
M. A. Storr
Abstract Background, Cannabinoid type 1 (CB1) receptors are involved in the regulation of gastrointestinal (GI) motility and secretion. Our aim was to characterize the roles of the CB1 receptor on GI motility and secretion in vitro and in vivo by using different classes of CB1 receptor antagonists. Methods, Immunohistochemistry was used to examine the localization of CB1 receptor in the mouse ileum and colon. Organ bath experiments on mouse ileum and in vivo motility testing comprising upper GI transit, colonic expulsion, and whole gut transit were performed to characterize the effects of the inverse agonist/antagonist AM251 and the neutral antagonist AM4113. As a marker of secretory function we measured short circuit current in vitro using Ussing chambers and stool fluid content in vivo in mouse colon. We also assessed colonic epithelial permeability in vitro using FITC-labeled inulin. Key Results,In vivo, the inverse agonist AM251 increased upper GI transit and whole gut transit, but it had no effect on colonic expulsion. By contrast, the neutral antagonist AM4113 increased upper GI transit, but unexpectedly reduced both colonic expulsion and whole gut transit at high, but not lower doses. Conclusions & Inferences, Cannabinoid type 1 receptors regulate small intestinal and colonic motility, but not GI secretion under physiological conditions. Cannabinoid type 1 inverse agonists and CB1 neutral antagonists have different effects on intestinal motility. The ability of the neutral antagonist not to affect whole gut transit may be important for the future development of CB1 receptor antagonists as therapeutic agents. [source]

Effect of otilonium bromide on contractile patterns in the human sigmoid colon

NEUROGASTROENTEROLOGY & MOTILITY, Issue 6 2010
D. Gallego
Abstract Background, The mechanism of action of the spasmolytic compound otilonium bromide (OB) on human colonic motility is not understood. The aim of our study was to characterize the pharmacological effects of OB on contractile patterns in the human sigmoid colon. Methods, Circular sigmoid strips were studied in organ baths. Isolated smooth muscle cells from human sigmoid colon were examined using the calcium imaging technique. Key Results, Otilonium bromide inhibited by 85% spontaneous non-neural rhythmic phasic contractions (RPCs), (IC50 = 49.9 nmol L,1) and stretch-induced tone (IC50 = 10.7 nmol L,1) with maximum effects at micromolar range. OB also inhibited by 50% both on- (IC50 = 38.0 nmol L,1) and off- contractions induced by electrical stimulation of excitatory motor neurons. In contrast, the inhibitory latency period prior to off -contractions was unaffected by OB. OB inhibited acetylcholine-, substance P-, and neurokinin A-induced contractions. The L-type Ca2+ channel agonist BayK8644 reversed the effects of OB on RPCs, on- and off -contractions. Hexamethonium, atropine, the NK2 antagonist, or depletion of intracellular Ca2+ stores by thapsigargin did not prevent the inhibitory effect of OB on RPCs and electrical contractions. KCl-induced calcium transients in isolated smooth muscle cells were also inhibited by OB (IC50 = 0.2 ,mol L,1). Conclusions & Inferences, Otilonium bromide strongly inhibited the main patterns of human sigmoid motility in vitro by blocking calcium influx through L-type calcium channels on smooth muscle cells. This pharmacological profile may mediate the clinically observed effects of the drug in patients with irritable bowel syndrome. [source]

Stimulatory action of mitemcinal (GM-611), an acid-resistant non-peptide motilin receptor agonist, on colonic motor activity and defecation: spontaneous and mitemcinal-induced giant migrating contractions during defecation in dogs

NEUROGASTROENTEROLOGY & MOTILITY, Issue 10 2009
T. Hirabayashi
Abstract, The aim of this study was to characterize giant migrating contractions (GMCs) during spontaneous defecation in dogs and to investigate the effect of mitemcinal (an orally active and highly acid-resistant motilin receptor agonist) on colonic motility to assess the possibility of using it for the treatment of colonic motility disorders. To assess colonic motility, strain-gauge force transducers were implanted on the gastrointestinal tract of five dogs, and the behaviour of the dogs was monitored with a noctovision-video camera system. The effect of mitemcinal (0, 3, 10 or 30 mg per dog) and sennoside (300 mg per dog) on colonic motility was assessed 24 h after oral administration. During a 39-day period, the starting point of most of the 140 GMCs was between the transverse colon and the descending colon, but some variation was observed. In the daytime, the GMCs originated from somewhat more proximal positions than at night. Mitemcinal caused an increase in the GMC-index (integration of contractile amplitude and duration) and proximal translocation of the GMC starting point, but did not cause an increase in the number of defecations 12 h after administration. Sennoside, however, caused a significant increase in the number of defecations, an increase in the GMC-index, and prolongation of the duration of GMCs. The GMC starting point in the canine colon varied during spontaneous defecation. Mitemcinal was a potent prokinetic drug to mimic a spontaneous defecation compared with sennoside. Mitemcinal evacuates more intestinal luminal contents during the defecation than does sennoside. [source]

Inhibitory effect of oxytocin on accelerated colonic motility induced by water-avoidance stress in rats

NEUROGASTROENTEROLOGY & MOTILITY, Issue 8 2009
M. Matsunaga
Abstract, Recent studies have indicated that brain and gut activities are interrelated and exposure to several stressors, such as water-avoidance stress, stimulates the motor function of the gut through corticotropin-releasing factor (CRF)-signalling pathways in the brain. Central oxytocin is known to attenuate stress responses, including CRF expression in the brain. Here, we examined whether central oxytocin attenuated the acceleration of colonic motility induced by water-avoidance stress. A force transducer was attached to the distal colon of male rat, and the colonic motility and faecal pellet output were recorded while the rats were exposed to water-avoidance stress. Intracerebroventricular (i.c.v.) injections of oxytocin (5, 50 and 500 pmol) and the oxytocin receptor antagonist tocinoic acid (25 ,g) were administered before exposure to water-avoidance stress, and the effect of oxytocin on colonic motor function was determined. Centrally administered oxytocin inhibited the accelerated colonic motility induced by water-avoidance stress. The effective dose ranged between 5 and 50 pmol on i.c.v. injection. Oxytocin also decreased the number of CRF-positive cells in the paraventricular nucleus and corticosterone release. The inhibitory effect of oxytocin on accelerated colonic motility was blocked by pretreatment with oxytocin receptor antagonist. Furthermore, centrally administered tocinoic acid enhanced the acceleration of colonic motility. These results suggested that endogenous central oxytocin may contribute to the regulation of colonic function and inhibit the brain CRF-signalling pathways targeting the gut, resulting in the inhibition of stress-induced colonic contractions. [source]

Cell-free supernatants of Escherichia coli Nissle 1917 modulate human colonic motility: evidence from an in vitro organ bath study

NEUROGASTROENTEROLOGY & MOTILITY, Issue 5 2009
F. Bär
Abstract, Clinical studies have shown that probiotics influence gastrointestinal motility, e.g. Escherichia coli Nissle 1917 (EcN) (Mutaflor®) proved to be at least as efficacious as lactulose and more potent than placebo in constipated patients. As the underlying mechanisms are not clarified, the effects of EcN culture supernatants on human colonic motility were assessed in vitro. Human colonic circular smooth muscle strips (n = 94, 17 patients) were isometrically examined in an organ bath and exposed to different concentrations of EcN supernatants. Contractility responses were recorded under (i) native conditions, (ii) electrical field stimulation (EFS), (iii) non-adrenergic non-cholinergic conditions, and (iv) enteric nerve blockade by tetrodotoxin (TTX). As concentrations of acetic acid were increased in EcN supernatants, contractility responses to acetic acid were additionally tested. EcN supernatants significantly increased the maximal tension forces both at low and high concentrations. Neither blockade of both adrenergic and cholinergic nerves nor application of TTX abolished these effects. EFS-induced contractility responses were not altered after exposure to EcN supernatants. Acetic acid elicited effects comparable to EcN supernatants only under TTX conditions. EcN supernatants modulate in vitro contractility of the human colon. As neither partial nor TTX blockade of enteric nerves abolished these effects, EcN supernatants appear to enhance colonic contractility by direct stimulation of smooth muscle cells. Active metabolites may include other substances than acetic acid, as acetic acid only partially resembled the effects elicited by EcN supernatants. The data provide a rationale for therapeutical application of probiotics in gastrointestinal motility disorders. [source]

Experimental pancreatitis disturbs gastrointestinal and colonic motility in mice: effect of the prokinetic agent tegaserod

NEUROGASTROENTEROLOGY & MOTILITY, Issue 10 2007
T. C. Seerden
Abstract, Acute pancreatitis remains a potentially life-threatening disease associated with gastrointestinal motility disturbances. Prokinetic agents may be useful to overcome these motility disturbances. In this study, we investigated the effect of acute necrotizing pancreatitis (ANP) on gastrointestinal motility in female mice and evaluated the effect of tegaserod, a prokinetic 5-hydroxytryptamine-4 (5HT4) receptor agonist. ANP was induced by feeding mice a choline-deficient ethionine-supplemented diet during 72 h. In vivo intestinal motility was measured as the geometric centre (GC) of 25 glass beads 30-120-360 min after gavage. Colonic peristaltic activity was studied using a modified Trendelenburg set-up. ANP significantly decreased GC 30-120-360 min after bead gavage, associated with a significant increase of myeloperoxidase in the proximal small intestine and colon, but not in the stomach or distal small intestine. Tegaserod significantly ameliorated GC 360 min after bead gavage in control and pancreatitis mice. In isolated colonic segments, ANP significantly decreased the amplitude of peristaltic waves and increased the interval between peristaltic contractions. Tegaserod normalized the disturbed interval. In conclusion, ANP impairs gastric, small intestinal and colonic motility in mice. Tegaserod improves ANP-induced motility disturbances in vivo and in vitro, suggesting a therapeutic benefit of prokinetic 5HT4 receptor agonists in the treatment of pancreatitis-induced ileus. [source]

Fibre-free diet leads to impairment of neuronally mediated muscle contractile response in rat distal colon

NEUROGASTROENTEROLOGY & MOTILITY, Issue 12 2006
R. Mitsui
Abstract, Dietary fibre consumption is known to be beneficial to increase stool bulk and frequency. In contrast, it is unclear whether chronic dietary fibre deficiency affects colonic motor functions, especially neuronally mediated muscle contractions. In this study, rats were fed a fibre-free diet or diet containing dietary fibre (cellulose or guar gum) for 27 days. Furthermore, neurogenic and myogenic contractions were evaluated in circular and longitudinal muscle strips of the distal colon. Additionally, the number of enterochromaffin (EC) cells, which play important roles in the initiation of the peristaltic reflex, was also examined by immunohistochemistry for serotonin. Myogenic contractions induced by carbachol or substance P were examined in the presence of tetrodotoxin. Circular muscle was hyposensitive to carbachol, but longitudinal muscle was hypersensitive to substance P in the fibre-free group. Nerve-mediated circular (5,20 Hz) and longitudinal (1,2 Hz) muscle contractions evoked by electrical field stimulation were attenuated in the fibre-free group and the latter response was almost abolished by atropine, suggesting functional changes of cholinergic neurons. EC cell number was decreased in the fibre-free group. In conclusion, changes in neurogenic and myogenic contractions and a decrease in EC cell number observed may affect colonic motility of the fibre-free group. [source]

Oxytocin stimulates colonic motor activity in healthy women

NEUROGASTROENTEROLOGY & MOTILITY, Issue 2 2004
B. Ohlsson
Abstract, The effects of oxytocin in the gastrointestinal tract are unclear. The aim of this study was to examine the effect of infusion of oxytocin on colonic motility and sensitivity in healthy women. Fourteen healthy women were investigated twice. A 6-channel perfusion catheter, with three recording points (2 cm apart) proximally and three recording points distally to a barostat balloon, was inserted to the splenic flexure. An intestinal feeding tube was placed in the mid-duodenum. A 90-min duodenal lipid infusion of 3 kcal min,1 was administered. Thirty minutes after the start of the lipid infusion, the subject randomly received either 20 or 40 mU min,1 of oxytocin, or isotonic saline as intravenous infusions for 90 min. Meanwhile, the colonic motility was recorded. During the last 30 min of oxytocin and saline infusion, the visceral sensitivity to balloon distensions was examined. During lipid infusion the number of antegrade contractions per hour was 0.7 ± 0.3 after saline and 3.9 ± 1.4 after oxytocin (P = 0.03), indicating more pronounced lumen-occlusive contractile activity after oxytocin administration. Some of these consisted of high-amplitude (> 103 mmHg in amplitude) antegrade contractions. Lipid infusion evoked a decrease of the balloon volume, reflecting increased colonic tone, but there was no difference between saline and oxytocin. Sensory thresholds did not differ significantly between saline and oxytocin. Infusion of oxytocin stimulates antegrade peristaltic contractions in stimulated colon in healthy women. The effects of oxytocin on colonic motor activity deserve to be further explored, especially in patients with colonic peristaltic dysfunction. [source]

Effects of female steroid hormones on A-type K+ currents in murine colon

Evaluation of laparoscopic surgery for Hirschsprung's disease from the standpoint of invasiveness and colonic motility: Prolapsing technique with extra-anal mucosectomy

ASIAN JOURNAL OF ENDOSCOPIC SURGERY, Issue 3 2009
Y Morikawa
Abstract Objective: Laparoscopic pull-through has become the standard surgical modality for Hirschsprung's disease in the field of pediatric surgery. This article discusses the minimal invasiveness of the prolapsing technique. This technique allows mucosectomies to be performed under direct vision even at the deepest dissected portion because the procedure is conducted via an extra-anal approach. Method: The laparoscopic prolapsing technique (Lap) is compared with the conventional open Soave technique in terms of the change in CRP and WBC, defecation function, both clinical and manometric, after surgery. Results: As a result, the timing of surgery has become earlier and the patients younger. Soiling occurs in 33% of open Soave and 0% of Lap patients. Manometry after Lap. pull-through revealed a positive recto-anal inhibitory reflex in 39% and evoked high amplitude propagated contraction was demonstrated in 85% of patients. Conclusion: These results suggest that the present technique, including minimal dissections of the mesentery and the preservation of pelvic nerves in combination with fine mucosectomy under direct vision, could be beneficial for postoperative anorectal function in patients with Hirschspurung's disease. [source]

5-HT4 receptors on cholinergic nerves involved in contractility of canine and human large intestine longitudinal muscle

BRITISH JOURNAL OF PHARMACOLOGY, Issue 5 2000
N H Prins
5-HT4 receptors mediate circular muscle relaxation in both human and canine large intestine, but this phenomenon alone can not explain the improvement in colonic motility induced by selective 5-HT4 receptor agonists in vivo. We set out to characterize 5-HT4 receptor-mediated effects in longitudinal muscle strips of canine and human large intestine. Electrical field stimulation (EFS) was applied providing submaximal isotonic contractions. L -NOARG (0.1 mM) was continuously present in the organ bath to preclude nitric oxide-induced relaxation to EFS. The selective 5-HT4 receptor agonist prucalopride (0.3 ,M) enhanced EFS-evoked contractions, that were antagonized in both preparations by the selective 5-HT4 receptor antagonist GR 113808 (0.1 ,M). The prucalopride-induced increase was present in canine ascending and descending colon, but absent in rectum. Regional differences in response to prucalopride were not observed in human ascending and sigmoid colon and rectum. Incubation with atropine (1 ,M) or tetrodotoxin (0.3 ,M) inhibited EFS-induced contractions, which were then unaffected by prucalopride (0.3 ,M) in both tissues. In the presence of methysergide (3 ,M; both tissues) and granisetron (0.3 ,M; only human tissues), 5-HT (0.3 ,M) enhanced EFS-induced contractions, an effect that was antagonized by GR 113808 (0.1 ,M). In the presence of atropine or tetrodotoxin, EFS-induced contractions were inhibited, leaving 5-HT (0.3 ,M) ineffective in both preparations. This study demonstrates for the first time that in human and canine large intestine, 5-HT4 receptors are located on cholinergic neurones, presumably mediating facilitating release of acetylcholine, resulting in enhanced longitudinal muscle contractility. This study and previous circular muscle strip studies suggest that 5-HT4 receptor agonism facilitates colonic propulsion via a coordinated combination of inhibition of circumferential resistance and enhancement of longitudinal muscle contractility. British Journal of Pharmacology (2000) 131, 927,932; doi:10.1038/sj.bjp.0703615 [source]